This research is designed to meet a critical need for a noninvasive, reliable, and cost-effective methemoglobin sensor. The long-term objective is to develop a commercial-grade sensor that provides realtime, point-of-care measurement of methemoglobin fraction in patients. High fractions of methemoglobin lead to tissue hypoxia and even death. Methemo-globinemia is commonly caused by environmental or work-related chemical exposures, and from pharmaceutical agents such as local anesthetics, acetaminophen, and drugs containing nitrites and/or nitrates. Children, especially those younger than four months of age, are particularly susceptible to methemoglobinemia. Treatment with inhaled nitric oxide for patients with respiratory failure has been shown to lead to increased methemoglobin levels, since the inhaled nitric oxide can combine with hemoglobin to form nitrosyl- hemoglobin, which is rapidly oxidized to methemoglobin. In the treatment of methemoglobinemia, it is necessary to be able to measure the methemoglobin fraction accurately. A noninvasive and reliable methemoglobin sensor will have great impact on therapeutic decision time. The specific aims of this Phase I project are (1) to develop a noninvasive methemoglobin sensor that incorporates the most current, state-of-the-art, inexpensive, reliable, and long-lasting light sources and detectors, (2) to design and develop algorithms for sensor operation and data analysis, utilizing phenomenological models that are based on first principles, (3) to conduct an animal study to demonstrate the feasibility and utility of the sensor and to examine the sensor performance, and (4) to perform a preliminary investigation of critical engineering, clinical, and regulatory issues that will contribute to the success of a Phase II. One area that has a potentially huge demand for noninvasive methemoglobin sensors is the Neonatal Intensive Care Units. The inhaled nitric oxide therapy effectively decreases the need for extracorporeal membrane oxygenation treatment. Since prolonged exposure to inhaled nitric oxide poses high risks for elevated methemoglobin levels, a realtime, noninvasive methemoglobin sensor will become an invaluable tool especially for neonates with limited blood volumes and/or difficult-to- established IV access. The sensor also has applications in transfusion medicine and in the defense against chemical warfare agents and cyanide poisoning. High concentrations of methemoglobin in blood lead to tissue hypoxia and even death. In the treatment of methemoglobinemia, it is critical to be able to measure the methemoglobin concentration accurately. A noninvasive and reliable methemoglobin sensor will have great impact on therapeutic decision time. [unreadable] [unreadable] [unreadable]